Platelets Disseminate Extracellular Vesicles in Lymph in Rheumatoid Arthritis

被引：47

作者：

Tessandier, Nicolas ^{[1
,2
]}

Melki, Imene ^{[1
,2
]}

Cloutier, Nathalie ^{[1
,2
]}

Allaeys, Isabelle ^{[1
,2
]}

Miszta, Adam ^{[3
,5
]}

Tan, Sisareuth ^{[4
]}

Milasan, Andreea ^{[7
]}

Michel, Sara ^{[1
,2
]}

Benmoussa, Abderrahim ^{[6
]}

Levesque, Tania ^{[1
,2
]}

Cote, Francine ^{[8
]}

McKenzie, Steven E. ^{[9
]}

Gilbert, Caroline ^{[1
,2
]}

Provost, Patrick ^{[1
,2
]}

Brisson, Alain R. ^{[4
]}

Wolberg, Alisa S. ^{[3
]}

Fortin, Paul R. ^{[1
,2
,10
]}

Martel, Catherine ^{[5
,7
]}

Boilard, Eric ^{[1
,2
,10
]}

机构：

[1] Ctr Rech CHU Quebec, Quebec City, PQ, Canada

[2] Univ Laval, Dept Microbiol Infectiol & Immunol, Quebec City, PQ, Canada

[3] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA

[4] Univ Bordeaux, CNRS, Extracellular Vesicles & Membrane Repair, IPB,CBMN,UMR 5248, Allee Geoffroy St Hilaire, Pessac, France

[5] Univ Montreal, Fac Med, Dept Med, Quebec City, PQ, Canada

[6] Univ Montreal, CHU St Justine, Dept Nutr, Quebec City, PQ, Canada

[7] Montreal Heart Inst, Quebec City, PQ, Canada

[8] Inserm U1163, Inst Imagine, Lab Olivier Hermine, Paris, France

[9] Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Philadelphia, PA 19107 USA

[10] Univ Laval, Ctr Rech CHU Quebec, Axe Malad Infect & Inflammatoires, Quebec City, PQ, Canada

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2020年 / 40卷 / 04期

基金：

加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

arthritis; extracellular vesicles; inflammation; leukocytes; lymphatic system; platelets; FC-GAMMA-RIIA; K/BXN MOUSE MODEL; ACTIVATED PLATELETS; INFLAMMATORY ARTHRITIS; R PACKAGE; IN-VITRO; RECEPTOR; MICROPARTICLES; VASCULATURE; GENE;

D O I：

10.1161/ATVBAHA.119.313698

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Objective: The lymphatic system is a circulatory system that unidirectionally drains the interstitial tissue fluid back to blood circulation. Although lymph is utilized by leukocytes for immune surveillance, it remains inaccessible to platelets and erythrocytes. Activated cells release submicron extracellular vesicles (EV) that transport molecules from the donor cell. In rheumatoid arthritis, EV accumulate in the joint where they can interact with numerous cellular lineages. However, whether EV can exit the inflamed tissue to recirculate is unknown. Here, we investigated whether vascular leakage that occurs during inflammation could favor EV access to the lymphatic system. Approach and Results: Using an in vivo model of autoimmune inflammatory arthritis, we show that there is an influx of platelet EV, but not EV from erythrocytes or leukocytes, in joint-draining lymph. In contrast to blood platelet EV, lymph platelet EV lacked mitochondrial organelles and failed to promote coagulation. Platelet EV influx in lymph was consistent with joint vascular leakage and implicated the fibrinogen receptor alpha 2b beta(3) and platelet-derived serotonin. Conclusions: These findings show that platelets can disseminate their EV in fluid that is inaccessible to platelets and beyond the joint in this disease.

引用

页码：929 / 942

页数：14

共 92 条

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CalDAG-GEFI deficiency protects mice from FcγRIIa-mediated thrombotic thrombocytopenia induced by CD40L and β2GPI immune complexes [J].